General Malaise and Physical Symptoms in Young Women with Untouched Toe

Untouched toe is a condition in which a toe does not touch the ground while standing. It is frequently observed in women even under physiological conditions. Deformities or symptoms of the toes are not observed in these women. The clinical significance of untouched toe has not been fully elucidated. Two hundred young healthy women were recruited into the present study after informed consent. We evaluated the prevalence of untouched toe by measuring various indexes of the toe using a foot-sole-measuring equipment. We also conducted a self-administered questionnaire regarding general malaise. Untouched toe was observed in 114 of these 200 women (57.0%). The fifth toe was more frequently affected than the other toes. There were no significant differences in size of foot except the area and proportion touching the ground between women with untouched toe and those without untouched toe. The prevalence of general malaise was significantly higher in women with at least one untouched toe (57.0%) compared with those without untouched toe (43.0%) (p＜0.05). Twelve symptoms―irritability, headache, tired eyes, hazy vision, congested or runny nose, irregular menstruation or menstrual pain, shoulder stiffness, neck stiffness, low back pain, cold hands, swollen feet, and cold feet―were more frequently observed in women with at least one untouched toe compared with those without untouched toes. Untouched toe was associated with various symptoms of general malaise. However, the pathological mechanism by which untouched toe causes these symptoms has not been determined. Further analysis of gait and exercise habits in women with untouched toe is necessary

The AMPA receptor antagonist perampanel robustly rescues amyotrophic lateral sclerosis (ALS) pathology in sporadic ALS model mice

Both TDP-43 pathology and failure of RNA editing of AMPA receptor subunit GluA2, are etiology-linked molecular abnormalities that concomitantly occur in the motor neurons of the majority of patients with amyotrophic lateral sclerosis (ALS). AR2 mice, in which an RNA editing enzyme adenosine deaminase acting on RNA 2 (ADAR2) is conditionally knocked out in the motor neurons, exhibit a progressive ALS phenotype with TDP-43 pathology in the motor neurons through a Ca2+-permeable AMPA receptor-mediated mechanism. Therefore, amelioration of the increased Ca2+ influx by AMPA receptor antagonists may be a potential ALS therapy. Here, we showed that orally administered perampanel, a selective, non-competitive AMPA receptor antagonist significantly prevented the progression of the ALS phenotype and normalized the TDP-43 pathology-associated death of motor neurons in the AR2 mice. Given that perampanel is an approved anti-epileptic drug, perampanel is a potential candidate ALS drug worthy of a clinical trial.UTokyo Research掲載「筋萎縮性側索硬化症の治療法に向けて」 URI: http://www.u-tokyo.ac.jp/ja/utokyo-research/research-news/finding-a-treatment-for-als.htmlUTokyo Research "Finding a treatment for ALS" URI: http://www.u-tokyo.ac.jp/en/utokyo-research/research-news/finding-a-treatment-for-als.htm

Calpain-dependent disruption of nucleo-cytoplasmic transport in ALS motor neurons

Nuclear dysfunction in motor neurons has been hypothesized to be a principal cause of amyotrophic lateral sclerosis (ALS) pathogenesis. Here, we investigated the mechanism by which the nuclear pore complex (NPC) is disrupted in dying motor neurons in a mechanistic ALS mouse model (adenosine deaminase acting on RNA 2 (ADAR2) conditional knockout (AR2) mice) and in ALS patients. We showed that nucleoporins (Nups) that constituted the NPC were cleaved by activated calpain via a Ca2+-permeable AMPA receptor-mediated mechanism in dying motor neurons lacking ADAR2 expression in AR2 mice. In these neurons, nucleo-cytoplasmic transport was disrupted, and the level of the transcript elongation enzyme RNA polymerase II phosphorylated at Ser2 was significantly decreased. Analogous changes were observed in motor neurons lacking ADAR2 immunoreactivity in sporadic ALS patients. Therefore, calpain-dependent NPC disruption may participate in ALS pathogenesis, and inhibiting Ca2+-mediated cell death signals may be a therapeutic strategy for ALS.UTokyo Research掲載「核と細胞質間の分子輸送経路の破綻が筋萎縮性側索硬化症に関与」 URI: http://www.u-tokyo.ac.jp/ja/utokyo-research/research-news/disruption-of-molecule-transport-pathway-between-nucleus-and-cytoplasm-involved-in-als.htmlUTokyo Research "Disruption of molecule transport pathway between nucleus and cytoplasm involved in ALS" URI: http://www.u-tokyo.ac.jp/en/utokyo-research/research-news/disruption-of-molecule-transport-pathway-between-nucleus-and-cytoplasm-involved-in-als.htm

The Quiescent Intracluster Medium in the Core of the Perseus Cluster

Clusters of galaxies are the most massive gravitationally-bound objects in the Universe and are still forming. They are thus important probes of cosmological parameters and a host of astrophysical processes. Knowledge of the dynamics of the pervasive hot gas, which dominates in mass over stars in a cluster, is a crucial missing ingredient. It can enable new insights into mechanical energy injection by the central supermassive black hole and the use of hydrostatic equilibrium for the determination of cluster masses. X-rays from the core of the Perseus cluster are emitted by the 50 million K diffuse hot plasma filling its gravitational potential well. The Active Galactic Nucleus of the central galaxy NGC1275 is pumping jetted energy into the surrounding intracluster medium, creating buoyant bubbles filled with relativistic plasma. These likely induce motions in the intracluster medium and heat the inner gas preventing runaway radiative cooling; a process known as Active Galactic Nucleus Feedback. Here we report on Hitomi X-ray observations of the Perseus cluster core, which reveal a remarkably quiescent atmosphere where the gas has a line-of-sight velocity dispersion of 164+/-10 km/s in a region 30-60 kpc from the central nucleus. A gradient in the line-of-sight velocity of 150+/-70 km/s is found across the 60 kpc image of the cluster core. Turbulent pressure support in the gas is 4% or less of the thermodynamic pressure, with large scale shear at most doubling that estimate. We infer that total cluster masses determined from hydrostatic equilibrium in the central regions need little correction for turbulent pressure.Comment: 31 pages, 11 Figs, published in Nature July

Hitomi (ASTRO-H) X-ray Astronomy Satellite

The Hitomi (ASTRO-H) mission is the sixth Japanese x-ray astronomy satellite developed by a large international collaboration, including Japan, USA, Canada, and Europe. The mission aimed to provide the highest energy resolution ever achieved at E  >  2  keV, using a microcalorimeter instrument, and to cover a wide energy range spanning four decades in energy from soft x-rays to gamma rays. After a successful launch on February 17, 2016, the spacecraft lost its function on March 26, 2016, but the commissioning phase for about a month provided valuable information on the onboard instruments and the spacecraft system, including astrophysical results obtained from first light observations. The paper describes the Hitomi (ASTRO-H) mission, its capabilities, the initial operation, and the instruments/spacecraft performances confirmed during the commissioning operations for about a month

Hitomi X-Ray Studies of Giant Radio Pulses from the Crab Pulsar

To search for giant X-ray pulses correlated with the giant radio pulses (GRPs) from the Crab pulsar, we performed a simultaneous observation of the Crab pulsar with the X-ray satellite Hitomi in the 2300 keV band and the Kashima NICT radio telescope in the 1.41.7 GHz band with a net exposure of about 2 ks on 2016 March 25, just before the loss of the Hitomi mission. The timing performance of the Hitomi instruments was confirmed to meet the timing requirement and about 1000 and 100 GRPs were simultaneously observed at the main pulse and inter-pulse phases, respectively, and we found no apparent correlation between the giant radio pulses and the X-ray emission in either the main pulse or inter-pulse phase. All variations are within the 2 fluctuations of the X-ray fluxes at the pulse peaks, and the 3 upper limits of variations of main pulse or inter-pulse GRPs are 22% or 80% of the peak flux in a 0.20 phase width, respectively, in the 2300 keV band. The values for main pulse or inter-pulse GRPs become 25% or 110%, respectively, when the phase width is restricted to the 0.03 phase. Among the upper limits from the Hitomi satellite, those in the 4.510 keV and 70300 keV bands are obtained for the first time, and those in other bands are consistent with previous reports. Numerically, the upper limits of the main pulse and inter-pulse GRPs in the 0.20 phase width are about (2.4 and 9.3) 10(exp 11) erg cm(exp 2), respectively. No significant variability in pulse profiles implies that the GRPs originated from a local place within the magnetosphere. Although the number of photon-emitting particles should temporarily increase to account for the brightening of the radio emission, the results do not statistically rule out variations correlated with the GRPs, because the possible X-ray enhancement may appear due to a >0.02% brightening of the pulse-peak flux under such conditions